| 19146434 |
Shaik N, Martinez A, Augustin I, Giovinazzo H, Varela-Ramirez A, Sanau M, Aguilera RJ, Contel M: Synthesis of Apoptosis-Inducing Iminophosphorane Organogold (III) Complexes and Study of Their Interactions with Biomolecular Targets. Inorg Chem. 2009 Feb 16;48(4):1577-87.
New stable cationic organogold (III) complexes containing the "pincer" iminophosphorane ligand (2-C (6) H (4)-PPh (2) NPh) have been prepared by reaction of the previously described [Au{kappa (2)-C,N-C (6) H (4)(PPh (2) N (C (6) H (5))-2}Cl (2)] 1 and a combination of sodium or silver salts and appropriate ligands. The presence of the P atom in the PR (3) fragment has been used as a "spectroscopic marker" to study the in vitro stability (and oxidation state) of the new organogold complexes in solvents like dimethyl sulfoxide and water. Compounds with dithiocarbamato ligands and water-soluble phosphines of the general type [Au{kappa (2)-C,N-C (6) H (4)(PPh (2) N (C (6) H (5))-2}(S (2) CN-R (2))] PF (6) (R = Me 2; Bz 3) and [Au{kappa (2)-C,N-C (6) H (4)(PPh (2) N (C (6) H (5))-2}(PR (3))(n) Cl] PF (6) (PR (3) = P{Cp (m-C (6) H (4)-SO (3) Na)(2)} n = 1 4, n = 2 TPA {1,3,5-triaza-7-phosphaadamantane} 5) have been synthesized and characterized in solution and in the solid state (the crystal structure of 2 has been determined by X-ray diffraction studies). Complexes 1-5 have been tested as potential anticancer agents, and their cytotoxicity properties were evaluated in vitro against HeLa human cervical carcinoma and Jurkat-T acute lymphoblastic leukemia cells. Compounds 2 and 3 are quite cytotoxic for these two cell lines. There is a preferential induction of apoptosis in HeLa cells after treatment with 1-5. However in the case of the more cytotoxic complex (2), cell death is activated because of both apoptosis and necrosis. The interactions of 1-5 with Calf Thymus DNA have been evaluated by Thermal Denaturation methods. All these complexes show no or little (electrostatic) interaction with DNA. The interaction of 2 with two model proteins (cytochrome c and thioredoxin reductase) has been analyzed by spectroscopic methods (vis-UV and fluorescence). Compound 2 manifests a high reactivity toward both proteins. The mechanistic implications of these results are discussed here. |
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